The treatment of psychiatric disorders by surgical means has an extensive history. In the early 1930""s, Fulton and Jacobsen first recognized that experimentally induced neurotic behavior in chimpanzees could be abolished by frontal lobectomy. Within a few years, Freeman and Watts developed the first psychosurgical procedure for humans known as the frontal lobotomy.
As the inherent physiology of the frontal lobe became more evident, the original freehand procedure of Freeman and Watts became less and less extensive. By the late 1940""s, the method of stereotaxis, in which the patient""s brain is modeled in 3-dimensional space for exquisite targeting accuracy, merged with lesioning techniques resulting in an even more efficacious and safe psychosurgical procedure. Further developments of stereotactic equipment have combined with novel advancements in functional and anatomic imaging as well as intraoperative electrophysiological mapping to encompass the state of the art in the neurosurgical treatment of neurological and psychiatric disorders today.
While technologically improved and more precise, today""s surgical lesioning techniques have the fundamental limitation of being inherently irreversible and are essentially a xe2x80x9cone shotxe2x80x9d procedure with little chance of alleviating or preventing potential side effects. In addition, there is a limited possibility to provide continuous benefits as the disease progresses and the patient""s symptoms evolve.
Within the field of neurosurgery, the use of electrical stimulation for treating neurological disease, including such disorders as movement disorders including Parkinson""s disease, essential tremor, dystonia, and chronic pain, has been widely discussed in the literature. It has been recognized that electrical stimulation holds significant advantages over lesioning, inasmuch as lesioning can only destroy nervous system tissue. In many instances, the preferred effect is to stimulate to increase, decrease, or block neuronal activity. Electrical stimulation permits such modulation of the target neural structures and, equally importantly, does not require the destruction of nervous tissue. In many ways, this is analogous to a reversible and adjustable lesioning procedure.
To date, however, disorders manifesting gross physical dysfunction, not otherwise determinable as having psychiatric and/or behavioral origins, comprise the vast majority of those pathologies treated by deep brain stimulation. A noteworthy example of treatment of a gross physical disorder by electrical stimulation is included in the work of Alim Benabid, who developed a method of reducing the tremor associated with Parkinson""s disease by the application of a high frequency electrical pulse directly to the thalamus. This has also been applied in the subthalamic nucleus for the treatment of Parkinson""s rigidity, slowness of movement, walking and other movement (see e.g. the New England Journal of Medicine, Vol. 339, October 1998, pp. 105-1111, Electrical Stimulation of the Subthalamic Nucleus in Advanced Parkinson""s Disease).
Efforts have been made to treat psychiatric disorders with peripheral/cranial nerve stimulation. A recent investigational protocol has demonstrated partial benefits with vagus nerve stimulation in patients with depression (Biological Psychiatry 47: 216-286, 2000) Additional clinical trials with depression and vagus nerve stimulation are underway. Another noteworthy example is the effort to control depression and compulsive eating disorders by stimulation of the vagus nerve is provided in U.S. Pat. No. 5,263,480. This treatment seeks to induce a satiety effect by stimulating the afferent vagal fibers of the stomach. For patients having weak emotional and/or psychological components to their eating disorders, this treatment can be effective insofar as it eliminates the additional (quasi-normal) physio-chemical stimulus to continue eating. This is especially true for patients who exhibit subnormal independent functioning of these fibers of the vagus nerve. For compulsive eating patients who are not suffering from an insufficient level of afferent vagal nerve activity resulting from sufficient food intake, however, the over stimulation of the vagus nerve and potential resultant over abundance of satiety mediating chemicals (cholecystokinin and pancreatic glucagon) may have little effect. It has even been suggested that continued compulsive eating, despite overstimulation of the vagus nerve, may exacerbate the emotional component of the patient""s disorder. This, therefore, begs the question, is vagus nerve stimulation useful in treating the psychological component of the disorder of compulsive eating, or is it simply a method of minimizing the additional, but natural, pressures to eat because of normal physical hunger. More generally, the question may be asked, is peripheral nerve stimulation of any kind the most appropriate method of treatment for disorders that are, at the core, the result of a pathology exhibited in the brain. The effect of this peripheral stimulation seems to be non-specific and a secondary phenomenon. Indeed functional brain imaging studies have demonstrated induction of intracranial thalamic activity thus providing evidence for an indirect action of the peripheral stimulators. A more appropriate target may be the brain region which is functioning abnormally.
Surgical treatments for psychiatric disorders that have traditionally been treated by behavioral therapy or psychiatric drugs, have been largely limited to the stereotactic lesioning such as cingulotomy, capsulotomy, subcaudate tractotomy, and limbic leucotomy. Such procedures have been applied to date in the treatment of affective disorders and anxiety disorders. If one critically examines the results of these procedures in the literature, it becomes apparent, when applied to a carefully selected patient population in conjunction with modern stereotactic surgical equipment and imaging techniques, that these procedures are both efficacious and safe. In fact, in a certain subset of patients who have failed all conventional treatments, these neurosurgical procedures may be the only treatment options available. Therefore, electrical and/or chemical neurosurgical neuromodulating techniques, with their inherent reversibility and adjustability, offer a safer and potentially more effective alternative to lesioning procedures. The present invention relates to modulation of neuronal activity to affect psychological or psychiatric activity. The present invention finds particular application in the modulation of neuronal function or processing to affect a functional outcome. The modulation of nueronal function is particularly useful with regard to the prevention, treatment, or modulation of psychiatric, psychological, behavioral, mood, and thought activity. (unless otherwise indicated these will be collectively referred to herein as xe2x80x9cpsychological activityxe2x80x9d or xe2x80x9cpsychiatric activityxe2x80x9d). When referring to a pathological or undesirable condition associated with the activity, reference may be made to xe2x80x9cpsychiatric disorderxe2x80x9d or xe2x80x9cpsychological disorderxe2x80x9d instead of psychiatric or psychological activity. Although the activity to be modulated usually manifests itself in the form of a disorder such as addiction/substance abuse, obsessive compulsive disorder, generalized anxiety disorder, post traumatic stress disorder, panic attacks, social phobia, major depression, bipolar disorder, schizophrenia, it is to be appreciated that the invention may also find application in conjunction with enhancing or diminishing any neurological or psychiatric function, not just abnormality or disorder. Psychiatric activity that may be modulated can include, but not be limited to, normal functions such as fear, anger, anxiety, euphoria, sadness, and the fight or flight response.
The present invention finds particular utility in its application to human psychological or psychiatric activity/disorder. However, it is also to be appreciated that the present invention is applicable to other animals which exhibit behavior that is modulated by the brain. This may include, for example, primates, canines, felines, elephants, dolphins, etc. Utilizing the various embodiments of the present invention, one skilled in the art may be able to modulate the functional outcome of the brain to achieve a desirable result.
One technique that offers the ability to affect neuronal function in a reversible and dynamic fashion is the delivery of electrical stimulation for neuromodulation directly to target tissues via an implanted electrode assembly.
Another technique that offers the ability to affect neuronal function in a reversible and dynamic fashion is the delivery of drugs or neuromodulating chemicals directly to target tissues via a subcutaneously implanted pump and/or a slow release matrix Such drugs, either traditional psychiatric agents or chemicals mimicking neurotransmitters, could be instilled precisely at such low doses as to completely avoid the side effects so common to modern pharmacotherapy and to provide a physiological neuromodulation. Such doses could also be tailored in magnitude with respect to a particular patient""s varying symptomatology. A chemical neuromodulating system may also be implanted as a primary treatment strategy or in combination with an electrically based one.
A combination therapeutic approach, one combining electrical and chemical means, would be penultimate to generating healthy neuronal tissue itself. In addition to the stimulation and chemical modulation, the implantable device could also have chemical and/or electrical sensing functions that can be coupled to the chemical and electrical output of the modulating device.
Initially there is an impetus to treat psychiatric disorders with direct modulation of activity in that portion of the brain causing the pathological behavior. In this regard there have been a large number of anatomical studies that have helped to identify the neural structures and their precise connections which are implicated in psychiatric activity/disorders. These are the structures that are functioning abnormally and manifesting in psychiatric/behavioral/addiction disorders. Numerous anatomical studies from autopsies, animal studies, and imaging such as computerized tomography (CT) scans, and magnetic resonance imaging (MRI) scans have demonstrated the role of these structures and their connections in psychiatric activity/disorders. In addition to these anatomical studies, a number of physiological techniques and diagnostic tools are used to determine the physiological aberrations underlying these disorders. This includes electrical methods such as electroencephalography (EEG), magnetoencephalography (MEG), as well as metabolic and blood flow studies such as functional magnetic resonance imaging (fMRI), and positron emission tomography (PET). The combination of the anatomical and physiological studies have provided increased insight into our understanding of the structures which are involved in the normal functioning or activity of the brain and the abnormal functioning manifesting in psychiatric, behavioral and addiction disorders.
The primary areas of interest for psychiatric acitivty/disorders include the pre-frontal cortex, orbitofrontal cortex, anterior limb of the internal capsule, Nucleus Accumbens, ventral striatum, the ventral Pallidum anterior nucleus of the thalamus, dorsomedial nucleus of the thalamus, intralaminar thalamic nuclei, the cingulate cortex, Amygdala, Hippocampus, Mamillary bodies, the lateral hypothlamus the Locus Ceruleus, the Dorsal Raphe Nucleus, ventral tegmentum, the Substantia Nigra Pars Compacta and reticulata. These structures are schematically shown in FIGS. 1 and 2 and are implicated in psychiatric activity and disorders.
One embodiment of the present invention relates generally to modulating the pathological electrical and chemical activity of the brain by electrical stimulation and/or direct placement of neuromodulating chemicals within the corresponding areas of abnormal function and activity. In accordance with this embodiment of the present invention, a method is provided which provides surgical treatment of psychiatric disorders (e.g. addictions/substance abuse, obsessive compulsive disorder, generalized anxiety disorder, post traumatic stress disorder, panic attacks, social phobia, major depression, bipolar disorder, schizophrenia, and addictions) by implantation of stimulating electrodes and/or drug/chemical delivery micro infusion at the locations detailed herein.
In another aspect, the present invention also provides methods for identifying the proper positioning of the electrodes and/or chemical/drug delivery catheters and microinfusion systems within the intralaminar nucleus in the thalamus to affect their associated connections in the thalamus and other subcortical and cortical areas such as the pre-frontal cortex, orbitofrontal cortex, anterior limb of the internal capsule, Nucleus Accumbens, ventral striatum, the ventral Pallidum, anterior nucleus of the thalamus, dorsomedial nucleus of the thalamus, intralaminar thalamic nuclei, the cingulate cortex, Amygdala, Hippocampus, Mamillary bodies, the lateral hypothlamus the Locus Ceruleus, the Dorsal Raphe Nucleus, ventral tegmentum, the Substantia Nigra Pars Compacta, and reticulata
In one embodiment of the invention, therefore, the proximal end of the electrode and/or catheter is coupled to an electrical signal source and/or drug delivery pump which, in turn, is operated to stimulate the predetermined treatment site in regions described above such that the functional outcome is achieve or the clinical effects of the psychiatric and disorders are reduced.
In an another embodiment of the present invention, a method of determining the proper therapeutic treatment (i.e., the proper position or placement of the electrodes and/or catheters) for a specific psychiatric, behavioral, addictive disorder comprising the steps of: identifying a large sampling of patients (each exhibiting a common specific psychiatric/addictive disorder or activity) and then identifying which common region of the brain exhibits pathological electrical and/or chemical activity during manifestations of the specific psychiatric disorder. The common regions demonstrating this pathological activity constitute the predetermined treatment site, wherefore a suitable means for affecting the activity of said predetermined treatment site may be employed to ameliorate/improve the psychiatric disorder/activity generically with a high probability of success.
In particular, the common regions identified above, are herein identified by their known anatomical connections and physiological functioning as being actively involved in channeling or generating the pathological electrical activity associated with psychiatric activity/disorders. It is important to note that these regions, including their functions and connections, are a common structural feature of human brains, and therefore is a common target across a large number of patients. As suggested above, this commonality of function and structure in these structures implicated in the psychiatric activity or disorder allows for common treatment targeting, even in instances wherein different patients have other disparate locations within their brains that also exhibit pathological electrical and/or metabolic activity.
In yet another embodiment of the present invention a method of treating a a specific psychiatric disorder is provided which is comprised of identifying the region of the ILN associated/interconnected with the areas (e.g. pre-frontal cortex or basal ganglia) manifesting the pathological electrical activity relating to the specific psychiatric disorder. These connections are demonstrated more fully in the detailed description below and the accompanying Figures. The common regions demonstrating this pathological activity constitute the predetermined treatment site, wherefore a suitable means for affecting the activity of said predetermined treatment site may be employed to ameliorate the psychiatric activity/disorder.
In yet another embodiment of the present invention, a method of treating an addiction associated with an area of interest in a brain comprising: implanting a probe in the area of interest, the probe including a chemical sensor and a chemical dispenser; coupling an end of the probe in fluid communication with the chemical dispenser to a chemical pump; and sensing in the area of interest a determined chemical condition; and operating the pump to urge a chemical through the chemical dispenser into the area of interest to thereby treat the addiction. The step of sensing may occur at a location distal from the device location, may occur at a distant site in the brain epidurally, subdurally, or from the scalp, or may be at the local milieu of the electrode and/or microinfusion cannula.
In yet another embodiment of the present invention, a method of treating an addiction associated with an area of interest in a brain comprising: implanting an electrode in the area of interest of a brain so that a distal end lies in communication with a predetermined site in the area of interest; coupling a proximal end of the electrode to at least one remotely located device; sensing electrical activity in the area of interest; and operating the electrode to provide electrical stimulation to the area of interest in response to the electrical activity to thereby treat the addiction.
In yet another embodiment of the present invention, a method of treating an addiction associated with an area of interest in a brain comprising: implanting an electrode in an intralaminar nucleus of a brain so that a distal end lies in communication with a predetermined site in the intralaminar nucleus; coupling a proximal end of the electrode to at least one remotely located device; sensing electrical activity in the area of interest; and operating the electrode to provide electrical stimulation to the intralaminar nucleus in response to the electrical activity to thereby treat the addiction.
In yet another embodiment of the present invention, a method of determining a treatment for, and subsequently treating a specific disorder comprising: identifying a set of patients, where the patients each exhibit a common specific disorder; placing a probe relative to a brain of at least one patient from the set of patients so that an end of the probe lies in communication with a treatment site in the brain; and operably connecting a second end of the probe to a remote device, where the remote device detects a specified condition in the treatment site and applies a corrective action based on the detected condition. The corrective action may increase thalamic activity or may decrease activity in the dorsomedial thalamus. The disorder may be selected from the group consisting of anxiety disorder, affective disorder, and substance abuse disorder.
In yet another embodiment of the present invention, a method of treating a disorder associated with a specific area in a brain comprising: implanting a device in contact with an intralaminar nuclei of the brain; sensing activity in a specific area of the brain; and operating the device to modulate the intralaminar nuclei in response to said activity to thereby affect the disorder associated with the specific area of the brain. The stimulation may be electrical, chemical or a combination thereof. The stimulation may be continuously, intermittently, or periodically. The specific area of the brain may be different than the intralaminar nuclei. The step of sensing may occur at a location distal from the device location, may occur at a distant site in the brain epidurally, subdurally, or from the scalp, or may be at the local milieu of the electrode and/or microinfusion cannula. The specific area may be selected from the group consisting of the pre-frontal cortex, orbitofrontal cortex, anterior limb of the internal capsule, Nucleus Accumbens, ventral striatum, the ventral Pallidum anterior nucleus of the thalamus, dorsomedial nucleus of the thalamus, intralaminar thalamic nuclei, the cingulate cortex, Amygdala, Hippocampus, Mamillary bodies, the lateral hypothlamus the Locus Ceruleus, the Dorsal Raphe Nucleus, ventral tegmentum, the Substantia Nigra Pars Compacta and reticulata. The psychiatric disorders may be selected from the group consisting of obsessive compulsive disorder, generalized anxiety disorder, post traumatic stress disorder, panic attacks, social phobia, major depression, bipolar disorder, schizophrenia, and substance abuse disorders/addictions.
In yet another embodiment of the present invention, a method of affecting a specific area in a brain comprising: placing an electrode in contact with an intralaminar nuclei of the brain; and operating the device to provide stimulation to the intralaminar nuclei to thereby affect the specific area of the brain. The stimulation may be electrical, chemical or a combination thereof. The stimulation may be continuously, intermittently, or periodically. The specific area of the brain may be different than the intralaminar nuclei. The step of sensing may occur at a location distal from the device location, may occur at a distant site in the brain epidurally, subdurally, or from the scalp, or may be at the local milieu of the electrode and/or microinfusion cannula. The specific area may be selected from the group consisting of the pre-frontal cortex, orbitofrontal cortex, anterior limb of the internal capsule, Nucleus Accumbens, ventral striatum, the ventral Pallidum anterior nucleus of the thalamus, dorsomedial nucleus of the thalamus, intralaminar thalamic nuclei, the cingulate cortex, Amygdala, Hippocampus, Mamillary bodies, the lateral hypothlamus the Locus Ceruleus, the Dorsal Raphe Nucleus, ventral tegmentum, the Substantia Nigra Pars Compacta and reticulate. The psychiatric disorders may be selected from the group consisting of obsessive compulsive disorder, generalized anxiety disorder, post traumatic stress disorder, panic attacks, social phobia, major depression, bipolar disorder, schizophrenia, and substance abuse disorders/addictions.
In yet another embodiment of the present invention, a method of effecting psychiatric activity in a patient comprising: identifying a portion of the patient""s ILN which is in communication with a predetermined region of the patient""s brain, said predetermined region of said patient""s brain being associated with the psychiatric activity; and modulating the portion of the patient""s ILN to effectuate the psychiatric activity. The identification of a portion of the patient""s ILN may already be identified. The identifying step may be independent of an exhibition of a pathologic condition in the predetermined region of said patient""s brain. The psychiatric activity may be selected from the group consisting of happiness, fear, anger, anxiety, euphoria, and sadness. The modulation of the portion of the patient""s ILN is accomplished using chemical stimulation, electrical stimulation, or combinations thereof.
Still further aspects of the present invention will become apparent to those of ordinary skill in the art upon reading and understanding the following detailed description of the preferred embodiments.